The objective of this project is to study the ACh-receptors purified from housefly brains and to compare their molecular properties and interactions with toxicants with available data on vertebrate ACh-receptors, so as to utilize differences found in the housefly brain ACh-receptors to synthesize toxicants that have higher affinities for them and test them for insecticidal and selective actions. The first step shall be to prove that the proteins isolated from housefly brain are indeed ACh-receptors by studying the effect of antibodies produced in rabbits against these proteins on cholinergic transmission in cockroach ganglia and investigate the microscopic localization of these antibodies (radiolabeled or fluorescent tagged) in the housefly brain and cockroach ganglia. The full binding activity shall be restored to these pure proteins and their molecular weight and shape shall be determined by chromatography, sedimentation equilibrium and electron microscopy. The amino acids shall be analyzed and the active groups and terminal amino groups assayed by active site-directed reagents and dansyl chloride, respectively. The subunits shall be determined by electrophoresis. If the housefly brain ACh-receptor is closely associated with an ion conductance modulator, attempts shall be made to identify this molecule through its binding of (3H)perhydrohistrionicotoxin. The interactions of the housefly ACh-receptors with various insecticides, particularly anticholinesterases, shall be determined by their effects on their binding of (3H)decamethonium studied by equilibrium dialysis, so as to establish if these ACh-receptors may be primary or secondary targets for these chemicals in insects.